sotorasib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| 5461 | 2296729-00-3 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models sotorasib-treatment led to tumor regressions and prolonged survival and was associated with anti-tumor immunity in KRAS G12C models.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
None
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Jan. 6, 2022 | EMA | Amgen Europe BV | |
| May 28, 2021 | FDA | AMGEN INC | |
| Jan. 20, 2022 | PMDA | AMGEN K.K. |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Non-small cell lung cancer | 157.02 | 65.97 | 24 | 184 | 3634 | 56288225 |
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Non-small cell lung cancer | 130.23 | 54.98 | 22 | 157 | 4087 | 31693078 |
FDA Adverse Event Reporting System (Geriatric)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Non-small cell lung cancer | 130.71 | 54.72 | 22 | 227 | 6325 | 70921870 |
| Death | 58.02 | 54.72 | 30 | 219 | 510031 | 70418164 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | L01XX73 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Other antineoplastic agents |
| MeSH PA | D000970 | Antineoplastic Agents |
| MeSH PA | D000074322 | Antineoplastic Agents, Immunological |
| MeSH PA | D000082082 | Immune Checkpoint Inhibitors |
| CHEBI has role | CHEBI:35610 | antineoplastic agents |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer | indication | 254637007 | DOID:3908 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
None
Orange Book patent data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent use |
|---|---|---|---|---|---|---|---|---|---|---|
| 120MG | LUMAKRAS | AMGEN INC | N214665 | May 28, 2021 | RX | TABLET | ORAL | 11236091 | May 20, 2040 | TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY |
| 120MG | LUMAKRAS | AMGEN INC | N214665 | May 28, 2021 | RX | TABLET | ORAL | 11426404 | Aug. 11, 2040 | TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY |
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| 120MG | LUMAKRAS | AMGEN INC | N214665 | May 28, 2021 | RX | TABLET | ORAL | May 28, 2026 | NEW CHEMICAL ENTITY |
| 120MG | LUMAKRAS | AMGEN INC | N214665 | May 28, 2021 | RX | TABLET | ORAL | May 28, 2028 | TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| GTPase KRas | Enzyme | INHIBITOR | IC50 | 7.03 | DRUG LABEL | DRUG LABEL |
External reference:
| ID | Source |
|---|---|
| D12055 | KEGG_DRUG |
| 2B2VM6UC8G | UNII |
| C5418250 | UMLSCUI |
| CHEBI:178199 | CHEBI |
| CHEMBL4535757 | ChEMBL_ID |
| 137278711 | PUBCHEM_CID |
| DB15569 | DRUGBANK_ID |
| 10678 | IUPHAR_LIGAND_ID |
| 347100 | MMSL |
| 39561 | MMSL |
| d09751 | MMSL |
| 4040545 | VANDF |
| 018747 | NDDF |
| 1162482008 | SNOMEDCT_US |
| 1162509004 | SNOMEDCT_US |
| C000706028 | MESH_SUPPLEMENTAL_RECORD_UI |
| 11370 | INN_ID |
| 2550714 | RXNORM |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| LUMAKRAS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 55513-488 | TABLET, COATED | 120 mg | ORAL | NDA | 28 sections |
| LUMAKRAS | HUMAN PRESCRIPTION DRUG LABEL | 1 | 55513-488 | TABLET, COATED | 120 mg | ORAL | NDA | 28 sections |